American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Garvey WT, Mechanick JI, Brett EM, et al. Endocrine practice: official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2016;22 Suppl 3:1-203.

The combined prevalence of overweight and obesity is 71% in adults 1, and up to 50 - 80% of obese men have testosterone deficiency (also known as hypogonadism).2,3 The most common comorbidity among the growing obese population is type 2 diabetes 4; about half of all men with type 2 diabetes have hypogonadism.3,5

Recent clinical guidelines on hypogonadism state that increased visceral body fat and obesity are signs of hypogonadism, and that testosterone should be assessed in men with obesity, metabolic syndrome and diabetes.6-8 However, due to the epidemic prevalence of overweight/obesity and related metabolic diseases, the large majority of hypogonadal men will see a primary care physician and/or a diabetologist or cardiologist, who is likely not aware of the clinical guidelines on hypogonadism.

It is therefore laudable that The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) Clinical Practice Guidelines for Comprehensive Medical Care of Patients with Obesity in their 2016 revision dedicated two comprehensive sections on testosterone deficiency and treatment. Here we summarize these AACE / ACE recommendations.9

Key Points

All men who have an increased waist circumference (≥102 cm) or who have obesity (BMI ≥30) should be assessed for hypogonadism by history and physical examination and be tested for testosterone deficiency; all men with hypogonadism should be evaluated for the presence of overweight or obesity.

All men with type 2 diabetes should be tested to exclude testosterone deficiency.

Treatment of hypogonadism in men with increased waist circumference or obesity should include weight-loss therapy. Weight loss of more than 5 to 10% is needed for significant improvement in serum testosterone.

Bariatric surgery should be considered as a treatment approach that improves hypogonadism in most patients with obesity, including patients with severe obesity (BMI >50 kg/m2) and type 2 diabetes.

Men with hypogonadism and obesity who are not seeking fertility should be considered for testosterone therapy in addition to lifestyle intervention, since testosterone in these patients results in weight loss, decreased waist circumference, and improvements in metabolic parameters glucose, HbA1C, lipids, and blood pressure).

What is known

The prevalence of obesity 1,10 and the metabolic syndrome 11 continues to rise, and so does the common obesity related comorbidity type 2 diabetes.12 Nearly 35% of all adults and 50% of those aged 60 years or older have the metabolic syndrome 11, and 38% are obese.1 In Western countries diabetes prevalence is 12%.13 Alarmingly, nearly 28% of the population has undiagnosed diabetes.13

While the prevalence of hypogonadism in primary care has been reported to be 10 - 39% 3,14, among obese men testosterone deficiency is up to 8 times more common.2,3 Obese men with or without the metabolic syndrome have around 150 and 300 ng/dL (5.2 and 10.4 nmol/L) lower testosterone levels compared to same aged lean men without metabolic syndrome.15 Based on these analyses, the presence of diabetes or fasting serum glucose greater than 110 mg/dL, BMI 30 kg/m2 or greater, and triglycerides 150 mg/dL or greater, each have a clinically relevant association with low serum testosterone.15

Physicians in primary care, diabetologists and cardiologists are unlikely to read hypogonadism specific guidelines. Therefore, the 2016 AACE/ACE clinical practice guideline – which targets health care professionals who are more likely to first encounter hypogonadal men - is a landmark publication.9

What the new AACE and ACE Clinical Practice Guideline recommends

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) Clinical Practice Guidelines for Comprehensive Medical Care of Patients with Obesity point out that there are strong associations between obesity, hypogonadism, and cardiometabolic disease, and conclude that sufficient evidence exists to include measurement of serum testosterone in the diagnostic evaluation of metabolic syndrome and type 2 diabetes.9 Obesity is covered in their executive summary: 9

All men who have an increased waist circumference (≥102 cm) or who have obesity (BMI ≥30 kg/m2) should be assessed for hypogonadism by history and physical examination and be tested for testosterone deficiency; all men with hypogonadism should be evaluated for the presence of overweight or obesity.

All men with type 2 diabetes should be tested to exclude testosterone deficiency.

Treatment of hypogonadism in men with increased waist circumference or obesity should include weight-loss therapy. Weight loss of more than 5 to 10% is needed for significant improvement in serum testosterone.

Bariatric surgery should be considered as a treatment approach that improves hypogonadism in most patients with obesity, including patients with severe obesity (BMI >50 kg/m2) and type 2 diabetes.

Men with hypogonadism and obesity who are not seeking fertility should be considered for testosterone therapy in addition to lifestyle intervention, since testosterone in these patients results in weight loss, decreased waist circumference, and improvements in metabolic parameters glucose, HbA1C, lipids, and blood pressure).

Comments

It is particularly notable that the AACE/ACE guideline recommends obese men with hypogonadism should be considered for testosterone therapy 9, as this acknowledges the relatively unknown vicious circle between obesity and hypogonadism.16,17

Bariatric surgery increases testosterone levels and may reverse hypogonadism.2 After bariatric surgery, the mean weight loss (baseline BMI 42 kg/m2) is maximal after 1 to 2 years (gastric bypass, 3%; vertical-banded gastroplasty, 25%; and banding, 20%). After 10 years, the weight losses is 25% for gastric bypass, 16% for vertical-banded gastroplasty, and 14% for banding, as compared with baseline eight.18 However, bariatric surgery is an invasive and expensive procedure that is not available to most patient. Bariatric surgery also confers a risk for serious complications.

In contrast, testosterone therapy – which is ubiquitously available at a fraction of the cost of bariatric surgery - safely reverses hypogonadism and results, if performed long-term and adequately, in a similar weight loss as bariatric surgery.19-27 A rapidly accumulating body of evidence is showing that testosterone therapy reduces fat mass and increases lean body mass, and in obese hypogonadal men results in concomitant weight loss with reduction in waist circumference and BMI.20,28-35 Long-term testosterone therapy for up to 10 years in obese men with testosterone deficiency results in a significant and marked sustained weight loss, and reduced waist circumference and BMI, without weight regain.20-27 A notable observational study of testosterone therapy in obese hypogonadal men found marked weight loss of 16.78%, 21.62% and 23.59% in obesity class I, class II and class III, respectively (figure 1).19

The 8 year long-term data of testosterone therapy in obese hypogonadal men 19 favorably compare with the 10 year data after bariatric surgery.18 Considering that bariatric surgery is an invasive and expensive procedure that can only treat a minority of the growing obese population, non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives.36

Further support for using testosterone therapy to treat obese hypogonadal men comes from research showing that long-term testosterone therapy for up to 10 years is safe and significantly and sustainably improves cardiometabolic parameters such as lipid profile, glycemic control, blood pressure, heart rate, and pulse pressure.20-22,27,37-40